Project Summary (Abstract) Nuclear molecular imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) have become important imaging modalities in the diagnosis and management of human diseases. Solid-state radiation detectors such as cadmium zinc telluride (CZT) have been developed for the detection of high-energy photons (x-ray and gamma-ray) including medical imaging systems by replacing more commonly used scintillation crystals (e.g., NaI or CsI) and photomultiplier tubes (PMTs). SPECT is a very mature noninvasive molecular imaging technology with many radiopharmaceuticals evaluated for many different medical conditions. However, its low detection efficiency and lack of 3D dynamic-imaging capability are mainly pointed out as disadvantages; thus there have been numerous efforts to replace all existing SPECT radiotracers with PET counterparts. SPECT brings much more flexibility in production of radiopharmaceuticals, and labeling biologically interesting molecules with 99mTc for SPECT imaging costs much less than production of PET radionuclides such as 18F using a medical cyclotron and labeling with 18F. However, the availability of many SPECT radiotracers in fact sometimes acts against the viability of SPECT technology because different SPECT radiotracers that emit different energies of photons (roughly in the range of 70 keV ? 350 keV) require change of collimators sometimes multiple times even during the same day in the clinical setting. Collimators not only limit the detection efficiency, but also hamper an efficient management of clinical imaging. With the previous funding support under ?Transforming Biomedicine at the Interface of the Life and Physical Sciences (R01)? (PAR-10- 141) which no longer exists, we developed a completely new SPECT technology that is based on high energy resolution CZT, redesigned and successfully fabricated application-specific integrated circuit (ASIC), and innovative collimator design that can cover a broad range of radionuclide emission energies. For this new grant application, we propose to bring in another very important system design innovation while further developing and manufacturing a prototype test system in that system design. The system innovation we are proposing is to have a variable aperture (i.e., small detector modules moving radially in and out) ring geometry so that we can image subjects within the field of view in high resolution (close proximity) in all possible angular positions. This design will also allow fast 3D dynamic imaging capability with no or almost no rotation (a few degrees). In order to achieve the goals defined above, we have the following specific aims: 1) To complete the variable aperture ring SPECT design using extensive Monte Carlo simulations; 2) To develop new ASICs to be combined with our small-pitch (1.6 mm) and modular CZT cameras that were developed by us recently. The new ASICs will allow list-mode acquisition, and high-count rate so that dynamic SPECT imaging can be handled efficiently. Direct list- mode reconstruction algorithms will be developed as well; and, 3) To build a prototype test system of at least one ring with a variable aperture.